In order to determine the effect of amoxicillin therapy on the perineal skin microbial flora in infants, we took quantitative bacterial and fungal cultures of perineal and sternal areas from 25 infants treated with amoxicillin (40 mg/kg/day) for 10 days. Specimens were obtained prior to therapy, within 3 days of conclusion of therapy, and 14-16 days later. Immediately following therapy, a decline in the number of bacterial isolates occurred on both the perineum (89 to 47) and sternum (84 to 39). The greatest decline occurred in the number of anaerobic bacteria (mostly Peptostreptococcus spp. and Propionibacterium acnes). Other organisms that were less often isolated were aerobic streptococci and Staphylococcus epidermidis. The number of Candida albicans isolates increased from 3 to 11 (p < 0.05) on the perineum, and 1 to 7 (p < 0.025) on the sternum. Four of the infants developed diaper dermatitis. The density of C. albicans increased more than 14-fold following amoxicillin therapy. Cultures done 14-16 days after cessation of therapy revealed an increase in the number of bacterial isolates on the perineum (47 to 72) and on the sternum (39 to 61) and a decline in recovery of C. albicans. This study demonstrates the effects of amoxicillin on the ecology of skin microbial flora in infants-a decrease in the number of bacterial isolates and an increase in recovery of C. albicans.